B6.129-Htt^tm5Mem/J

Stock number: 003598
Product name: Hdh^Q111
Strain synonyms: HdhQ111 KI
Research areas: Mouse/Human Gene Homologs, Neurobiology Research

Description

These Hdh^Q111 knock-in mice exhibit Huntington's-like pathology.

As of November 2024, The Jackson Laboratory Stock No. 003598 will use breeders with CAG repeat expansion range of ~102-116 and distribute mice with CAG repeat expansion range of ~100-120 [range scoring as determined by Transnetyx assay].

Detailed description

Hdh^Q111 was created with 111 CAG repeat units in the first exon of the endogenous Htt gene. Huntington's-like pathology is seen in the striatum, including nuclear localization of the protein, N-terminal inclusions, and insoluble aggregate formation.

Expression of the Htt^tm5 phenotype occurs earlier than in Htt^tm4 (Stock No. 003455).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

CAG Repeat monitoring:
The CAG repeat number is subject to germline/somatic instability and may expand/contract. As such, the CAG repeat expansion size should be monitored in breeders at every generation. If labs do not have access to the appropriate equipment for determining CAG repeat length, CAG repeats can be evaluated on a fee-for-service basis by Laragen, Inc.

Stock No. 003598 B6.129-Htt^tm5Mem/J - Trinucleotide Scoring and Range [November 2024]:
 As of 2023, The Jackson Laboratory will use breeders with CAG repeat expansion range of ~103-117 and distribute mice with CAG repeat expansion range of ~101-121 [range scoring as determined by Laragen assay].
 In 2024, The Jackson Laboratory scoring of this strain's trinucleotide (CAG) repeat values was changed to Transnetyx following their acquisition of Laragen. Subsequently, The Jackson Laboratory Genetic Quality Control group and Transnetyx performed side-by-side CAG repeat value analyses of the same homozygous mouse samples (representing several different pedigrees within the live colony) via the Laragen protocol versus the Transnetyx protocol. For Stock No. 003598, more than 125 mouse samples were analyzed - this showed the Laragen score averaging 1.18 trinucleotide repeats higher than the same sample scored via Transnetyx. Based on these analyses, The Jackson Laboratory has adjusted the trinucleotide score range we use for Stock No. 003598 homozygous breeder mice from 103-117 CAG repeats via Laragen protocol to 102-116 CAG repeats via Transnetyx protocol, and homozygous distribution mice from 101-121 CAG repeats via Laragen protocol to 100-120 CAG repeats via Transnetyx protocol [November 2024].

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes and 111 CAG repeat units was used to disrupt exon 1. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to CD1 mice, and then backcrossed to C57BL/6J for 6 generations.
MGI Mutation Details for this Htt^tm5Mem allele states "It is a derivative of Htt^tm8 in which the neo cassette has been removed via cre-mediated recombination."

Stock No. 003598 B6.129-Htt^tm5Mem/J - Trinucleotide Scoring and Range [November 2024]:
 As of 2023, The Jackson Laboratory will use breeders with CAG repeat expansion range of ~103-117 and distribute mice with CAG repeat expansion range of ~101-121 [range scoring as determined by Laragen assay].
 In 2024, The Jackson Laboratory scoring of this strain's trinucleotide (CAG) repeat values was changed to Transnetyx following their acquisition of Laragen. Subsequently, The Jackson Laboratory Genetic Quality Control group and Transnetyx performed side-by-side CAG repeat value analyses of the same homozygous mouse samples (representing several different pedigrees within the live colony) via the Laragen protocol versus the Transnetyx protocol. For Stock No. 003598, more than 125 mouse samples were analyzed - this showed the Laragen score averaging 1.18 trinucleotide repeats higher than the same sample scored via Transnetyx. Based on these analyses, The Jackson Laboratory has adjusted the trinucleotide score range we use for Stock No. 003598 homozygous breeder mice from 103-117 CAG repeats via Laragen protocol to 102-116 CAG repeats via Transnetyx protocol, and homozygous distribution mice from 101-121 CAG repeats via Laragen protocol to 100-120 CAG repeats via Transnetyx protocol [November 2024].

Allele

Symbol: Htt^tm5Mem
Name: targeted mutation 5, Marcy E MacDonald
MGI accession ID: MGI:1861935
Generation method: Targeted
Attributes: Humanized sequence
Synonyms: Hdh^Q111
Marker symbol: Htt
Marker name: huntingtin
Marker synonyms: C430023I11Rik; Hd; Hdh; htt; IT15; LOMARS
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: This allele carries 109 CAG repeat units, with 111 glutamines, in the first exon of the endogenous gene. It is a derivative of Htt^tm8 in which the neo cassette has been removed via cre-mediated recombination.